Insight Into HIV Transmission Risk When the Viral Load Is Undetectable and No Condom Is Used

The sexual transmission of HIV occurs after an exposure to fluids that contain HIV, such as semen and fluids from the vagina and rectum. The amount of virus in these fluids (also known as viral load) is the most important factor that determines whether an exposure to HIV will lead to infection. Research shows that a higher viral load increases the risk of HIV transmission and that a lower viral load decreases the risk.

The viral load in the blood of a person living with HIV is measured regularly to monitor the success of antiretroviral therapy (also called ART). Successful ART can reduce the viral load in the blood and other bodily fluids to undetectable levels, which can reduce the risk of sexual transmission. ART therefore represents an important new HIV prevention tool, which also has the potential to reduce the guilt, blame and anxiety associated with the possibility of transmitting HIV to a partner.

Gaps in the Evidence

Several studies released over the past few years have confirmed that ART has HIV prevention benefits. The most well-known study is the randomized-controlled clinical trial known as HPTN 052. In this study, early initiation of ART reduced the risk of HIV transmission by 96% among heterosexual serodiscordant couples. However, the couples who participated in this study reported having mostly vaginal sex, so the reduction in HIV risk for anal sex remained unclear.

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While HPTN 052 showed that ART can dramatically reduce the risk of HIV transmission through vaginal sex, the actual risk of HIV transmission (i.e., what the risk is lowered to) when the blood viral load is undetectable remained unknown, particularly for condomless sex.

Fortunately, two ongoing studies are investigating these unanswered questions. The studies are aiming to determine the actual risk of HIV transmission (for condomless vaginal and anal sex) when the HIV-positive partner's blood viral load is undetectable. Preliminary results from one of these studies -- the PARTNER Study -- were released at the recent Conference on Retroviruses and Opportunistic Infections (CROI) held in Boston in March 2014. These results are the first to provide direct evidence that ART can reduce the risk of HIV transmission during anal sex.

The PARTNER Study

The PARTNER study is a large observational study that is following serodiscordant couples at over 70 HIV clinics in 14 European countries. All of the couples enrolled:

are either heterosexual or gay men

consist of one HIV-negative partner and one HIV-positive partner who is on ART

do not use condoms regularly

The study began in September 2010 and is ongoing.

Once enrolled, the HIV-positive partner must commit to receiving their HIV care from the study clinic and both partners are required to attend the clinic every six months. At each visit, the HIV-positive partner's viral load is measured, the HIV-negative partner's HIV status is checked, and both partners are asked to complete a questionnaire about their sexual behaviour in the past six months. The HIV-positive partner also receives additional care, such as STI testing and information on the importance of adherence to ART, and both partners are told about the importance of using condoms to reduce the risk of HIV transmission.

If an HIV-negative partner becomes infected with HIV, a genetic analysis of the virus is performed. This is done to confirm that the virus was transmitted by the HIV-positive partner enrolled in the study and not by someone else outside of the relationship.

Results

The preliminary results presented at CROI are part of a planned interim analysis. They are based on information from couples, followed up until November 2013, that met the following criteria:

report of condomless sex

an undetectable viral load in the HIV-positive partner (defined as less than 200 copies per ml of blood)

no use of PEP or PrEP by the HIV-negative partner

Of the 1,110 couples recruited by November 2013, 767 met the above criteria. This included 282 same-sex male couples, 245 heterosexual couples where the HIV-positive partner was female, and 240 heterosexual couples where the HIV-positive partner was male. Overall, couples contributed a total of 894 couple-years of follow-up (equivalent to following 894 couples for a year).

At the start of the study, the HIV-positive partners had been on ART for an average of 5 years and couples had been having condomless sex for an average of 2 years.

During the preliminary study period, eligible couples reported condomless sex an average of 45 times a year (approximately once a week). This ranged from 16 times a year to 90 times a year. Same-sex male couples had sex more often than heterosexual couples. Same-sex male couples were also more likely to have a partner outside of the relationship (34% vs. 3% for heterosexual couples) and have a sexually transmitted infection (16% vs. 5%).

Between September 2010 and November 2013, the couples reported more than 44,000 condomless sex acts. These included:

13,728 receptive vaginal sex acts (the HIV-negative partner receiving the HIV-positive partner's penis into their vagina) with or without ejaculation

Despite the large number of condomless sex acts, no HIV transmissions occurred between any of the couples enrolled in the study. However, some of the HIV-negative partners did become infected with HIV by a person outside of the relationship.

Since there was no control group in the PARTNER trial, it is difficult to know how many HIV transmissions would have occurred if the HIV-positive partner was not on ART and did not have an undetectable viral load. However, using information from previous studies, researchers estimated that 15 HIV infections in heterosexual couples and 86 among same-sex male couples would have occurred if the HIV-positive partner had not been on ART.

The PARTNER study represents the first direct evidence that ART can reduce the risk of HIV transmission for same-sex male couples.

Understanding and Measuring Certainty

The fact that no transmissions occurred in this study is very encouraging. However, as with any research finding, it is important to consider the role that chance may have played. This is particularly important when investigating HIV transmission risk, because the average risk of HIV infection can be relatively low in some cases, regardless of viral load. The lower the risk, the more difficult it is to measure accurately. In general, the larger the study, the more confident researchers can be that the results are real and did not occur due to chance.

One way of measuring certainty is to use confidence limits. Confidence limits take into account the potential effects of chance and suggest a range of values that likely encompass the "true" risk. In the PARTNER study, investigators calculated upper confidence limits for the risk of HIV transmission per sex act and over time. The "upper confidence limit" provides an estimate of the highest possible transmission risk that is consistent with the study results.

For this study, upper confidence limits can be interpreted as follows:

It is extremely likely that the "true" risk is somewhere between 0% and the upper confidence limit.

It is extremely unlikely that the "true" risk is above the upper confidence limit.

The upper confidence limit is particularly important when a study finds zero risk because it gives some indication of how close to zero the "true" risk is likely to be.

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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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